Pathophysiology of Heart Failure: Role of Oxygen Free Radicals

Abstract

Oxygen free radicals (OFRs) are known to produce a decrease in cardiac function and contractility. The decrease in cardiac contractility and function in chronic volume overload heart failure might be due to an increased level of OFRs and/or decrease in the antioxidant status. We, therefore, studied the effects of chronic volume overload in the absence and presence of vitamin E (antioxidant) on cardiac function and contractility, cardiac malondialdehyde (MDA), a lipid peroxidation product and a fingerprint for levels of OFRs, cardiac antioxidant enzyme activity and antioxidant reserve in canine model. Volume overload heart failure was produced by creating mitral regurgitation (MR). Volume overload produced a decrease in the index of myocardial contractility manifested by an increase in left ventricular end diastolic pressure LVEDP without a significant change in cardiac index (CI). There was an increase in pulmonary vascular resistance (PVR) and total systemic vascular resistance (TSVR).The decrease in cardiac contractility was associated with an increase in cardiac MDA and a decrease in cardiac antioxidant reserve and antioxidant enzyme activity. Prevention of volume overload induced decrease in cardiac contractility by vitamin E was associated with a decrease in cardiac MDA and an increase in cardiac antioxidant reserve and glutathione peroxidase activity towards control levels. Superoxide dismutase and catalase activity remained depressed in vitamin E-treated animals. These results suggest that the oxygen free radicals are involved in the chronic volume overload heart failure.